(1) Field of the Invention
The present invention relates to a degradable 1,4-benzodioxepin-3-hexyl-2,5-dione monomer derived polymer. The homopolymer has a high glass transition temperature. Also, the invention relates to heteropolymers from this monomer.
(2) Description of Related Art
In the discovery and development of biodegradable plastics, aliphatic polyesters, such as polylactide (1Dechy-Cabaret, O.; Martin-Vaca, B.; Bourissou, D. Chem. Rev. 2004, 104, 6147-6176) and poly(3-hydroxybutyrate); and (2Lenz, R. W.; Marchessault, R. H. Biomacromolecules 2005, 6, 1-8), have played a key role (3Mecking, S. Angewandte Chemie-International Edition 2004, 43, 1078-1085). However, modern polyester industry is still dominated by aromatic polyesters, e.g. poly(ethylene terephalate) (PET) and poly(butylene terephalate) (PBT), because of their excellent thermal and mechanical properties, high chemical resistance and extremely low gas permeability. Now, the relative stability and biological inertness of these aromatic polyesters are becoming a major drawback, especially in the area of disposable materials, such as widely used non-degradable PET-based beverage bottles. According to EPA, in 2003 only 5.2% of rubber in municipal solid waste was recovered in the United States in 2003.
In an attempt to combine the excellent material properties of aromatic polyesters with the potential biodegradability of aliphatic polyesters, a number of aliphatic-aromatic polyesters have been developed. For example, both BASF and Eastman Chemical are currently marketing biodegradable polyesters of terephthalic acid and adipic acid with 1,4-butanediol under the trade names of Ecoflex™ and Eastar Bio™, respectively. Generally, aliphatic-aromatic polyester is made by copolymerizing aromatic diacid (mostly terephthalic acid) and aliphatic diacid (adipic acid, sebacic acid, or fumaric acid) with aliphatic diol (ethylene glycol, PEG-diol, or 1,4-cyclohexanedimethanol) via polycondensation reaction.
However, incorporating flexible aliphatic ester chains into rigid aromatic polyesters to introduce degradability greatly reduces Tg and Tm. Compared to PET (Tg=78° C., Tm=260° C.), (4Kint, D. P. R.; Munoz-Guerra, S. Polym. Int. 2003, 52, 321-336) Ecoflex has much lower Tg (−30° C.) and Tm (110-115° C.), (3Mecking, S. Angewandte Chemie-International Edition 2004, 43, 1078-1085). As a result, the use temperatures of aliphatic-aromatic polyesters are severely compromised, and their low Tg and high crystallinity will inevitably limit their uses as rigid, clear replacements for large-volume thermoplastics such as polystyrene. Furthermore, the polycondensation reaction applied in synthesizing aliphatic-aromatic polyester is accompanied by low molecular weight, high polydispersity, and poor regioselectivity control of the polymer structure.
Although the ring-opening polymerization of cyclic oligomers to form PET has been realized, (5Nagahata, R.; Sugiyama, J.; Goyal, M.; Asai, M.; Ueda, M.; Takeuchi, K. J. Polym. Sci., Part A: Polym. Chem. 2000, 38, 3360-3368); (6Nagahata, R.; Sugiyama, J. J.; Goyal, M.; Goto, M.; Honda, K.; Asai, M.; Ueda, M.; Takeuchi, K. Polymer 2001, 42, 1275-1279); (7Youk, J. H.; Boulares, A.; Kambour, R. P.; MacKnight, W. J. Macromolecules 2000, 33, 3600-3605), aliphatic-aromatic polyester synthesized by ring-opening polymerization is very rare. An exceptional way of mimicking aliphatic-aromatic polyester with better thermal stability but also utilizing ring-opening polymerization to fine control the polymer structure was patented (U.S. Pat. No. 5,082,925 to Shalaby et al) (Scheme 1) (Shalaby, S. W.; Koelmel, D. F.; Arnold, S. U.S. Pat. No. 5,082,925 (1992)). In vitro and in vivo degradations showed that this polymer is completely biodegradable.
wherein R is hydrogen or methylScheme 1. Synthesis and degradation of poly(1,4-benzodioxepin-2,5(3H)-dione) and poly(1,4-benzodioxepin-2,5(3H)-3-methyl-dione.
Another important feature of poly(1,4-benzodioxepin-2,5(3H)-dione) is that its degradation releases therapeutically active salicylic acid, as does aspirin. In this aspect, it shows very similar feature as that of well-studied salicylate-based poly(anhydride esters). (8Schmeltzer, R. C.; Schmalenberg, K. E.; Uhrich, K. E. Biomacromolecules 2005, 6, 359-367); (9Prudencio, A.; Schmeltzer, R. C.; Uhrich, K. E. Macromolecules 2005, 38, 6895-6901); (10Schmeltzer, R. C.; Anastasiou, T. J.; Uhrich, K. E. Polym. Bull. 2003, 49, 441-448); (11Anastasiou, T. J.; Uhrich, K. E. J. Polym. Sci., Part A: Polym. Chem. 2003, 41, 3667-3679); and (12Bedell, C.; Deng, M.; Anastasiou, T. J.; Uhrich, K. E. J. Appl. Polym. Sci. 2001, 80, 32-38). In both cases drug is released upon the hydrolysis of the polymer backbone, and degradation profiles, as well as physical properties such as Tg, can be manipulated by incorporating different linkers. See references: (13Auras, R.; Harte, B.; Selke, S. Macromol. Biosci. 2004, 4, 835-864); (14Liu, T. Q.; Simmons, T. L.; Baker, G. L. Polymeric Materials: Science & Engineering 2003, 88, 420); (24Aggarwal, V. K.; Thomas, A.; Schade, S. Tetrahedron 1997, 53, 16213-16228); (25Masamune, S.; Choy, W.; Kerdesky, F. A. J.; Imperiali, B. Journal of the American Chemical Society 1981, 103, 1566-1568).